The present invention relates to novel amino-acid derivatives, to their use as pharmaceuticals, and to their preparation. More particularly, the compounds of the invention are 2-cyanoethyl-substituted N-benzoylaminoalkanoic acid derivatives which possess immunoregulatory and anti-tumor activities.
In the literature, Knobler Y. et al., J. Chem. Soc. C. (14) 1821-4 (1969), discloses N-(substituted benzoyl) glutamic acid derivatives which have a 2-carboxyethyl substituent in place of the 2-cyanoethyl substituent of the compounds of the present invention; Wakamatsu H. et al., J. Chem. Soc. D. Chem. Commun., (23) 1540 (1971), discloses the compound 2-(2-cyanoethyl)-N-acetylglycine; and Pichat L. et al., Bull. Soc. Chim. Fr. 1970(5) 1837-8, discloses, as an intermediate for amino acid synthesis, the compound 2-(3-cyanopropyl)-N-benzoylglycine. However, no immunoregulatory or anti-tumor activity is disclosed for any of these compounds. On the other hand, Umezawa H. et al., J. Antibiotics 29(8), 857-859 (1976), discloses the compound "bestatin", which is [(2S, 3R)-3-amino-2-hydroxy-4-phenylbutanoyl]-L-leucine, which is said to exhibit host-mediated anti-tumor activity; but the structure of this compound differs markedly from that of the compounds provided by the present invention. Lastly, Kobayashi S. et al., in "Synthesis and Immulogical Activities of Muramyl Dipeptide Derivatives", presented at the 7th Symposium on Progress in Organic Reactions and Synthesis, in Gifu, Japan, in 1980 reports dipeptides having immunological activity and expected to have anti-tumor activity; but again these differ in structure from the compounds of the present invention.
Thus, to the best of our knowledge, the literature does not disclose any immunoregulatory or anti-neoplastic agents with a structure of the type possessed by the compounds which we now provide.